ER stress: Autophagy induction, inhibition and selection

Cell proliferation is a key determinant of the outcome of FOXO3a activation

(2015) Raewyn C. Poulsen et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Autophagy and protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2 alpha kinase (eIF2α) pathway protect ovarian cancer cells from metformin-induced apoptosis

(2015) Hee-sun Moon et al.   MOLECULAR CARCINOGENESIS

Regulation of endoplasmic reticulum turnover by selective autophagy

(2015) Aliaksandr Khaminets et al.   NATURE

Receptor-mediated selective autophagy degrades the endoplasmic reticulum and the nucleus

(2015) Keisuke Mochida et al.   NATURE

A Role for Macro-ER-Phagy in ER Quality Control

(2015) Zhanna Lipatova et al.   PLoS Genetics

Two hits are better than one: targeting both phosphatidylinositol 3-kinase and mammalian target of rapamycin as a therapeutic strategy for acute leukemia treatment

(2015) Alberto M. Martelli et al.   Oncotarget

Induction of macroautophagy by exogenously introduced calcium

(2014) Wentao Gao et al.   Autophagy

Regulation of ER stress-induced macroautophagy by protein kinase C

(2014) Kenjiro Sakaki et al.   Autophagy

Dual Role of JNK1-mediated phosphorylation of Bcl-2 in autophagy and apoptosis regulation

(2014) Yongjie Wei et al.   Autophagy

Endoplasmic reticulum stress induced by tunicamycin and thapsigargin protects against transient ischemic brain injury

(2014) Xiangnan Zhang et al.   Autophagy

The membrane peroxin PEX3 induces peroxisome-ubiquitination-linked pexophagy

(2014) Shun-ichi Yamashita et al.   Autophagy

Endoplasmic reticulum stress-mediated autophagy protects against lipopolysaccharide-induced apoptosis in HL-1 cardiomyocytes

(2014) Xiaojing Zou et al.   EXPERIMENTAL PHYSIOLOGY

Dissection of the role of p62/Sqstm1 in activation of Nrf2 during xenophagy

(2014) Ryosuke Ishimura et al.   FEBS LETTERS

Ubiquitin-specific protease-14 reduces cellular aggregates and protects against mutant huntingtin-induced cell degeneration: involvement of the proteasome and ER stress-activated kinase IRE1 

(2014) A. Hyrskyluoto et al.   HUMAN MOLECULAR GENETICS

Bufalin Induces the Interplay between Apoptosis and Autophagy in Glioma Cells through Endoplasmic Reticulum Stress

(2014) Shuying Shen et al.   International Journal of Biological Sciences

Where is mTOR and what is it doing there?

(2014) Charles Betz et al.   JOURNAL OF CELL BIOLOGY

ER-phagy mediates selective degradation of endoplasmic reticulum independently of the core autophagy machinery

(2014) S. Schuck et al.   JOURNAL OF CELL SCIENCE

Regulation of the Death-Associated Protein Kinase 1 Expression and Autophagy via ATF6 Requires Apoptosis Signal-Regulating Kinase 1

(2014) P. Gade et al.   MOLECULAR AND CELLULAR BIOLOGY

Quality Control Autophagy Degrades Soluble ERAD-Resistant Conformers of the Misfolded Membrane Protein GnRHR

(2014) Scott A. Houck et al.   MOLECULAR CELL

Endoplasmic reticulum stress and cell death in mTORC1-overactive cells is induced by nelfinavir and enhanced by chloroquine

(2014) Charlotte E. Johnson et al.   Molecular Oncology

Endoplasmic Reticulum Stress-Mediated Activation of p38 MAPK, Caspase-2 and Caspase-8 Leads to Abrin-Induced Apoptosis

(2014) Ritu Mishra et al.   PLoS One

Lysosome: regulator of lipid degradation pathways

(2014) Carmine Settembre et al.   TRENDS IN CELL BIOLOGY

Impaired autophagic flux is associated with increased endoplasmic reticulum stress during the development of NAFLD

(2014) Á González-Rodríguez et al.   Cell Death & Disease

Modulation of intracellular calcium homeostasis blocks autophagosome formation

(2013) Nikolai Engedal et al.   Autophagy

Chronic Akt activation attenuated lipopolysaccharide-induced cardiac dysfunction via Akt/GSK3β-dependent inhibition of apoptosis and ER stress

(2013) Maolong Dong et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

Activation of lysosomal function in the course of autophagy via mTORC1 suppression and autophagosome-lysosome fusion

(2013) Jing Zhou et al.   CELL RESEARCH

Nrf2 and Nrf1 signaling and ER stress crosstalk: implication for proteasomal degradation and autophagy

(2013) Hadi Digaleh et al.   CELLULAR AND MOLECULAR LIFE SCIENCES

Intracellular signaling in ER stress-induced autophagy in skeletal muscle cells

(2013) Luca Madaro et al.   FASEB JOURNAL

p38MAPK-regulated induction of p62 and NBR1 after photodynamic therapy promotes autophagic clearance of ubiquitin aggregates and reduces reactive oxygen species levels by supporting Nrf2–antioxidant signaling

(2013) Noemí Rubio et al.   FREE RADICAL BIOLOGY AND MEDICINE

Ultraviolet (UV) and Hydrogen Peroxide Activate Ceramide-ER Stress-AMPK Signaling Axis to Promote Retinal Pigment Epithelium (RPE) Cell Apoptosis

(2013) Jin Yao et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Alternative fates of newly formed PrPSc upon prion conversion on the plasma membrane

(2013) R. Goold et al.   JOURNAL OF CELL SCIENCE

Functional and morphological impact of ER stress on mitochondria

(2013) Kayleen Vannuvel et al.   JOURNAL OF CELLULAR PHYSIOLOGY

Forkhead box class O transcription factors in liver function and disease

(2013) Irina Tikhanovich et al.   JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY

AMPK involvement in endoplasmic reticulum stress and autophagy modulation after fatty liver graft preservation: a role for melatonin and trimetazidine cocktail

(2013) Mohamed Amine Zaouali et al.   JOURNAL OF PINEAL RESEARCH

Nelfinavir and bortezomib inhibit mTOR activity via ATF4-mediated sestrin-2 regulation

(2013) Ansgar Brüning et al.   Molecular Oncology

ER-stress-induced transcriptional regulation increases protein synthesis leading to cell death

(2013) Jaeseok Han et al.   NATURE CELL BIOLOGY

The eIF2α/ATF4 pathway is essential for stress-induced autophagy gene expression

(2013) Wafa B’chir et al.   NUCLEIC ACIDS RESEARCH

Role of Intracellular Calcium in Proteasome Inhibitor-Induced Endoplasmic Reticulum Stress, Autophagy, and Cell Death

(2013) Jessica A. Williams et al.   PHARMACEUTICAL RESEARCH

The lysosome: from waste bag to potential therapeutic target

(2013) Hanna Appelqvist et al.   Journal of Molecular Cell Biology

Pathways to decoding the clinical potential of stress response FOXO-interaction networks for Huntington's disease: of gene prioritization and context dependence

(2013) Frédéric Parmentier et al.   Frontiers in Aging Neuroscience

Oxidized lipids activate autophagy in a JNK-dependent manner by stimulating the endoplasmic reticulum stress response

(2013) Petra Haberzettl et al.   Redox Biology

IFNG and autophagy

(2012) Dhananjaya V. Kalvakolanu et al.   Autophagy

Induction of REDD1 gene expression in the liver in response to endoplasmic reticulum stress is mediated through a PERK, eIF2α phosphorylation, ATF4-dependent cascade

(2012) Scot R. Kimball et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

The role of ALFY in selective autophagy

(2012) P Isakson et al.   CELL DEATH AND DIFFERENTIATION

Silencing of Lipid Metabolism Genes through IRE1α-Mediated mRNA Decay Lowers Plasma Lipids in Mice

(2012) Jae-Seon So et al.   Cell Metabolism

Endoplasmic reticulum protein BI-1 regulates Ca2+-mediated bioenergetics to promote autophagy

(2012) R. Sano et al.   GENES & DEVELOPMENT

Reduced cathepsins B and D cause impaired autophagic degradation that can be almost completely restored by overexpression of these two proteases in Sap C-deficient fibroblasts

(2012) M. Tatti et al.   HUMAN MOLECULAR GENETICS

Targeting the UPR transcription factor XBP1 protects against Huntington's disease through the regulation of FoxO1 and autophagy

(2012) Rene L. Vidal et al.   HUMAN MOLECULAR GENETICS

AKT inhibition mitigates GRP78 (glucose-regulated protein) expression and contribution to chemoresistance in endometrial cancers

(2012) Michael J. Gray et al.   INTERNATIONAL JOURNAL OF CANCER

XBP1mRNA Splicing Triggers an Autophagic Response in Endothelial Cells throughBECLIN-1Transcriptional Activation

(2012) Andriana Margariti et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

ER stress–mediated autophagy promotes Myc-dependent transformation and tumor growth

(2012) Lori S. Hart et al.   JOURNAL OF CLINICAL INVESTIGATION

Modulation of glutamine metabolism by the PI(3)K–PKB–FOXO network regulates autophagy

(2012) Kristan E. van der Vos et al.   NATURE CELL BIOLOGY

Structure of the human ATG12~ATG5 conjugate required for LC3 lipidation in autophagy

(2012) Chinatsu Otomo et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Activation of AMP-Activated Protein Kinase Inhibits Albumin-Induced Endoplasmic Reticulum Stress and Apoptosis through Inhibition of Reactive Oxygen Species

(2012) Eun Kyoung Lee et al.   NEPHRON EXPERIMENTAL NEPHROLOGY

Regulation of autophagy during ECM detachment is linked to a selective inhibition of mTORC1 by PERK

(2012) A Avivar-Valderas et al.   ONCOGENE

GRP78 Knockdown Enhances Apoptosis via the Down-Regulation of Oxidative Stress and Akt Pathway after Epirubicin Treatment in Colon Cancer DLD-1 Cells

(2012) Yu-Jia Chang et al.   PLoS One

Autophagy Induced by Calcium Phosphate Precipitates Involves Endoplasmic Reticulum Membranes in Autophagosome Biogenesis

(2012) Xi Chen et al.   PLoS One

ER Stress Activates NF-κB by Integrating Functions of Basal IKK Activity, IRE1 and PERK

(2012) Arvin B. Tam et al.   PLoS One

Chaperone-mediated autophagy: a unique way to enter the lysosome world

(2012) Susmita Kaushik et al.   TRENDS IN CELL BIOLOGY

Bidirectional crosstalk between endoplasmic reticulum stress and mTOR signaling

(2012) Christian Appenzeller-Herzog et al.   TRENDS IN CELL BIOLOGY

Metformin Accelerates the Growth of BRAF V600E -Driven Melanoma by Upregulating VEGF-A

(2012) Matthew J. Martin et al.   Cancer Discovery

Biogenesis and Cargo Selectivity of Autophagosomes

(2011) Hilla Weidberg et al.   Annual Review of Biochemistry

Thapsigargin distinguishes membrane fusion in the late stages of endocytosis and autophagy

(2011) Ian G. Ganley et al.   Autophagy

Selective autophagy mediated by autophagic adapter proteins

(2011) Terje Johansen et al.   Autophagy

BAG3 and friends: Co-chaperones in selective autophagy during aging and disease

(2011) Christian Behl   Autophagy

Activation of ER stress and apoptosis by hydrogen peroxide in HeLa cells: Protective role of mild heat preconditioning at 40°C

(2011) Pragathi Pallepati et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

NBR1 and p62 as cargo receptors for selective autophagy of ubiquitinated targets

(2011) Trond Lamark et al.   CELL CYCLE

mTORC1 serves ER stress-triggered apoptosis via selective activation of the IRE1–JNK pathway

(2011) H Kato et al.   CELL DEATH AND DIFFERENTIATION

Autophagy: for better or for worse

(2011) Ellen Wirawan et al.   CELL RESEARCH

Cell Differentiation: Midbody Remnants — Junk or Fate Factors?

(2011) Kay O. Schink et al.   CURRENT BIOLOGY

JNK regulates FoxO-dependent autophagy in neurons

(2011) P. Xu et al.   GENES & DEVELOPMENT

IRE1 plays an essential role in ER stress-mediated aggregation of mutant huntingtin via the inhibition of autophagy flux

(2011) Huikyong Lee et al.   HUMAN MOLECULAR GENETICS

PERK Integrates Autophagy and Oxidative Stress Responses To Promote Survival during Extracellular Matrix Detachment

(2011) A. Avivar-Valderas et al.   MOLECULAR AND CELLULAR BIOLOGY

Distinct Autophagosomal-Lysosomal Fusion Mechanism Revealed by Thapsigargin-Induced Autophagy Arrest

(2011) Ian G. Ganley et al.   MOLECULAR CELL

Ca2+/Calmodulin-Dependent Kinase (CaMK) Signaling via CaMKI and AMP-Activated Protein Kinase Contributes to the Regulation of WIPI-1 at the Onset of Autophagy

(2011) S. G. Pfisterer et al.   MOLECULAR PHARMACOLOGY

AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1

(2011) Joungmok Kim et al.   NATURE CELL BIOLOGY

Regulation of glucose homeostasis through a XBP-1–FoxO1 interaction

(2011) Yingjiang Zhou et al.   NATURE MEDICINE

Regulation of AKT Phosphorylation at Ser473 and Thr308 by Endoplasmic Reticulum Stress Modulates Substrate Specificity in a Severity Dependent Manner

(2011) Hong Wa Yung et al.   PLoS One

Postfertilization Autophagy of Sperm Organelles Prevents Paternal Mitochondrial DNA Transmission

(2011) S. Al Rawi et al.   SCIENCE

The Unfolded Protein Response: From Stress Pathway to Homeostatic Regulation

(2011) P. Walter et al.   SCIENCE

ER Stress Inhibits mTORC2 and Akt Signaling Through GSK-3 -Mediated Phosphorylation of Rictor

(2011) C.-H. Chen et al.   Science Signaling

Modulating stress responses by the UPRosome: A matter of life and death

(2011) Ute Woehlbier et al.   TRENDS IN BIOCHEMICAL SCIENCES

Endoplasmic-Reticulum Calcium Depletion and Disease

(2011) D. Mekahli et al.   Cold Spring Harbor Perspectives in Biology

Macroautophagy Is Regulated by the UPR–Mediator CHOP and Accentuates the Phenotype of SBMA Mice

(2011) Zhigang Yu et al.   PLoS Genetics

ER stress negatively regulates AKT/TSC/mTOR pathway to enhance autophagy

(2010) Liang Qin et al.   Autophagy

The TSC1 and TSC2 tumor suppressors are required for proper ER stress response and protect cells from ER stress-induced apoptosis

(2010) Y J Kang et al.   CELL DEATH AND DIFFERENTIATION

AMPK-independent induction of autophagy by cytosolic Ca2+ increase

(2010) Antje Grotemeier et al.   CELLULAR SIGNALLING

The role of the Atg1/ULK1 complex in autophagy regulation

(2010) Noboru Mizushima   CURRENT OPINION IN CELL BIOLOGY

Fighting disease by selective autophagy of aggregate-prone proteins

(2010) Helene Knaevelsrud et al.   FEBS LETTERS

The RUN Domain of Rubicon Is Important for hVps34 Binding, Lipid Kinase Inhibition, and Autophagy Suppression

(2010) Qiming Sun et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Role of Inositol Trisphosphate Receptors in Autophagy in DT40 Cells

(2010) M. Tariq Khan et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Zymophagy, a Novel Selective Autophagy Pathway Mediated by VMP1-USP9x-p62, Prevents Pancreatic Cell Death

(2010) Daniel Grasso et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

FYCO1 is a Rab7 effector that binds to LC3 and PI3P to mediate microtubule plus end–directed vesicle transport

(2010) Serhiy Pankiv et al.   JOURNAL OF CELL BIOLOGY

Autophagy Regulates Endoplasmic Reticulum Homeostasis and Calcium Mobilization in T Lymphocytes

(2010) W. Jia et al.   JOURNAL OF IMMUNOLOGY

Autophagy: cellular and molecular mechanisms

(2010) Danielle Glick et al.   JOURNAL OF PATHOLOGY

Induction of Liver Steatosis and Lipid Droplet Formation in ATF6α-Knockout Mice Burdened with Pharmacological Endoplasmic Reticulum Stress

(2010) Keisuke Yamamoto et al.   MOLECULAR BIOLOGY OF THE CELL

Autophagy in mammalian development and differentiation

(2010) Noboru Mizushima et al.   NATURE CELL BIOLOGY

Eaten alive: a history of macroautophagy

(2010) Zhifen Yang et al.   NATURE CELL BIOLOGY

Mechanisms of mitophagy

(2010) Richard J. Youle et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy

(2010) D. F. Egan et al.   SCIENCE

LKB1 and AMP-activated protein kinase control of mTOR signalling and growth

(2009) R. J. Shaw   Acta Physiologica

Regulation Mechanisms and Signaling Pathways of Autophagy

(2009) Congcong He et al.   Annual Review of Genetics

XBP-1 deficiency in the nervous system reveals a homeostatic switch to activate autophagy

(2009) Soledad Matus et al.   Autophagy

NBR1 co-operates with p62 in selective autophagy of ubiquitinated targets

(2009) Vladimir Kirkin et al.   Autophagy

A novel, human Atg13 binding protein, Atg101, interacts with ULK1 and is essential for macroautophagy

(2009) Carol A. Mercer et al.   Autophagy

Selective types of autophagy in yeast

(2009) Claudine Kraft et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

The Role of ATF4 Stabilization and Autophagy in Resistance of Breast Cancer Cells Treated with Bortezomib

(2009) M. Milani et al.   CANCER RESEARCH

RETRACTED: VMA21 Deficiency Causes an Autophagic Myopathy by Compromising V-ATPase Activity and Lysosomal Acidification

(2009) Nivetha Ramachandran et al.   CELL

Mammalian autophagy: core molecular machinery and signaling regulation

(2009) Zhifen Yang et al.   CURRENT OPINION IN CELL BIOLOGY

Atf4 regulates chondrocyte proliferation and differentiation during endochondral ossification by activating Ihh transcription

(2009) W. Wang et al.   DEVELOPMENT

Mitochondria-Anchored Receptor Atg32 Mediates Degradation of Mitochondria via Selective Autophagy

(2009) Koji Okamoto et al.   DEVELOPMENTAL CELL

Atf4 Regulates Obesity, Glucose Homeostasis, and Energy Expenditure

(2009) J. Seo et al.   DIABETES

The structure of Atg4B–LC3 complex reveals the mechanism of LC3 processing and delipidation during autophagy

(2009) Kenji Satoo et al.   EMBO JOURNAL

DAP-kinase-mediated phosphorylation on the BH3 domain of beclin 1 promotes dissociation of beclin 1 from Bcl-XL and induction of autophagy

(2009) Einat Zalckvar et al.   EMBO REPORTS

Activating transcription factor 4 and CCAAT/enhancer-binding protein-β negatively regulate the mammalian target of rapamycin via Redd1 expression in response to oxidative and endoplasmic reticulum stress

(2009) Hyeon-Ok Jin et al.   FREE RADICAL BIOLOGY AND MEDICINE

XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy

(2009) C. Hetz et al.   GENES & DEVELOPMENT

SCAMP5 Links Endoplasmic Reticulum Stress to the Accumulation of Expanded Polyglutamine Protein Aggregates via Endocytosis Inhibition

(2009) Jee-Yeon Noh et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Coordination of membrane events during autophagy by multiple class III PI3-kinase complexes

(2009) Anne Simonsen et al.   JOURNAL OF CELL BIOLOGY

Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells

(2009) María Salazar et al.   JOURNAL OF CLINICAL INVESTIGATION

The unfolded protein response protects human tumor cells during hypoxia through regulation of the autophagy genes MAP1LC3B and ATG5

(2009) Kasper M.A. Rouschop et al.   JOURNAL OF CLINICAL INVESTIGATION

Activation of the Akt-NF- B Pathway by Subtilase Cytotoxin through the ATF6 Branch of the Unfolded Protein Response

(2009) H. Yamazaki et al.   JOURNAL OF IMMUNOLOGY

Tuberous Sclerosis Complex Activity Is Required to Control Neuronal Stress Responses in an mTOR-Dependent Manner

(2009) A. Di Nardo et al.   JOURNAL OF NEUROSCIENCE

A Role for NBR1 in Autophagosomal Degradation of Ubiquitinated Substrates

(2009) Vladimir Kirkin et al.   MOLECULAR CELL

A Genetic Screen in Drosophila Reveals Novel Cytoprotective Functions of the Autophagy-Lysosome Pathway

(2009) Andrew M. Arsham et al.   PLoS One

Function of IRE1 alpha in the placenta is essential for placental development and embryonic viability

(2009) T. Iwawaki et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Inclusion-body myositis: muscle-fiber molecular pathology and possible pathogenic significance of its similarity to Alzheimer’s and Parkinson’s disease brains

(2008) Valerie Askanas et al.   ACTA NEUROPATHOLOGICA

DAP-kinase is a mediator of endoplasmic reticulum stress-induced caspase activation and autophagic cell death

(2008) D Gozuacik et al.   CELL DEATH AND DIFFERENTIATION

Dynein-dependent Movement of Autophagosomes Mediates Efficient Encounters with Lysosomes

(2008) Shunsuke Kimura et al.   CELL STRUCTURE AND FUNCTION

FoxO transcription factors in the maintenance of cellular homeostasis during aging

(2008) Dervis AM Salih et al.   CURRENT OPINION IN CELL BIOLOGY

Roles of IP3R and RyR Ca2+ Channels in Endoplasmic Reticulum Stress and  -Cell Death

(2008) D. S. Luciani et al.   DIABETES

HspB8 Participates in Protein Quality Control by a Non-chaperone-like Mechanism That Requires eIF2α Phosphorylation

(2008) Serena Carra et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Protein Kinase Cθ Is Required for Autophagy in Response to Stress in the Endoplasmic Reticulum

(2008) Kenjiro Sakaki et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

JNK1-Mediated Phosphorylation of Bcl-2 Regulates Starvation-Induced Autophagy

(2008) Yongjie Wei et al.   MOLECULAR CELL

Messenger RNA targeting to endoplasmic reticulum stress signalling sites

(2008) Tomás Aragón et al.   NATURE

Autophagy fights disease through cellular self-digestion

(2008) Noboru Mizushima et al.   NATURE

Beclin1-binding UVRAG targets the class C Vps complex to coordinate autophagosome maturation and endocytic trafficking

(2008) Chengyu Liang et al.   NATURE CELL BIOLOGY

Novel targets for Huntington's disease in an mTOR-independent autophagy pathway

(2008) Andrea Williams et al.   Nature Chemical Biology

The pivotal role of c-Jun NH2-terminal kinase-mediated Beclin 1 expression during anticancer agents-induced autophagy in cancer cells

(2008) D-D Li et al.   ONCOGENE

The FoxO code

(2008) D R Calnan et al.   ONCOGENE

Autophagy Is Essential for Preimplantation Development of Mouse Embryos

(2008) S. Tsukamoto et al.   SCIENCE